Nodal Cytotoxic Lymphoma Spectrum

Abstract

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).

Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas

“…This signature is in accordance with previous data, since it comprises genes already described as overexpressed in ALCL such as MCL-1 (Rassidakis et al, 2002(Rassidakis et al, , 2003Villalva et al, 2002), CTLA1-granzyme B (Kagami et al, 1999), TP53 (Petit et al, 2001) and JUNB (Villalva et al, 2002). Some features of our ALCL signature, like overexpression of IL13R, FOS and JUNB, suggest a Th2 differentiation (Mao et al, 2003), which is also in accordance with previous IHC findings (Tsuchiya et al, 2004).…”

“…Some of these genes are known to be expressed in ALCL, such as CTLA1-GZMB, FOS, JUN, MCL-1 and IL13RA2 (Kagami et al, 1999;Petit et al, 2001;Rassidakis et al, 2002;Villalva et al, 2002). The T-LBL cluster (orange) contained genes involved in cell proliferation (PCNA, CDC2, E2F1, CDKN2A, Ki67, MADH2, MAX, MYC, CDK2, CDK4, CDK10, CDK8), cell-cycle (TP53BP2, TP53, CCNA1, CCND3) and cytoskeleton biology (tubulins A1, B2, B4, G1).…”

Cytotoxic T-cell and NK-cell Lymphomas

“…Although often CD4 + , anaplastic large cell lymphoma is a usually cytotoxic neoplasm that can present in the GI tract or other extranodal sites. 68–72…”

Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis

“…Some of these cases were included in extranodal NKTCL series [44,50] and in series of patients with cytotoxic lymphomas [51]. For instance, in a review of 49 Asian cases of CD56+ neoplasms from which 34 were NKTCL, one had a primary nodal presentation [50] and a Brazilian series of 122 cases NKTCL, from which 23 cases were extranasal, included 6 nodal cases [44].…”

“…For instance, in a review of 49 Asian cases of CD56+ neoplasms from which 34 were NKTCL, one had a primary nodal presentation [50] and a Brazilian series of 122 cases NKTCL, from which 23 cases were extranasal, included 6 nodal cases [44]. In another series of 66 patients with nodal cytotoxic cell lymphomas, one had the classic NKTCL phenotype [51]. In addition, cases of nodal lymphomas with a typical NKTCL phenotype and T-cell receptor (TCR) gamma ( TCRG ) gene rearrangements in germ-line configuration were described as case reports [48,49].…”